Systemic lupus erythematosus (SLE) is a chronic, inflammatory, often multisystemic disease which can be acute or insidious in onset. SLE is marked by a wide variety of abnormalities, including arthritis and arthralagias, nephritis, central nervous system manifestations, pleurisy, pericarditis, leukopenia or thrombocytopenia, and hemolytic anemia. One of the most serious complications of SLE is lupus nephritis. Renal involvement usually occurs early in the course of the illness and is the leading cause of death in SLE patients.
Diagnosis of SLE is made on the basis of a number of clinical symptoms such as the so-called "butterfly rash," an erythematous rash which frequently appears on the cheeks of afflicted individuals, crossing the bridge of the nose and becoming more pronounced upon exposure to sunlight; and arthritis which can affect any joint system. However, diagnosis is difficult to verify without appropriate laboratory tests. In this regard, antibodies directed to double-stranded DNA (dsDNA) are diagnostic of SLE and serum titers correlate with disease activity in both humans and mice (Pearson et al., J.Immunol. 126:16 (1981)).
Although the role of DNA as the significant target antigen of the so called "anti-dsDNA antibodies" which are diagnostic of SLE, is controversial, it is accepted that the anti-dsDNA antibodies play a significant part in the pathogenesis of the disease, especially its nephritic manifestations, e.g. a secreted form of an anti-dsDNA antibody encoded on a transgene was shown to cause SLE-like glomerulonephritis in a nonautoimmune mouse (Tsao et al., J.Immunol. 149:350 (1992)). Furthermore, the high level and wide variety of autoantibodies against nuclear constituents, especially DNA, and cytoplasmic cellular components detectable in afflicted individuals suggests that the disease represents a failure of the regulatory mechanisms of the autoimmune system that sustain self-tolerance and prevent the body from attacking its own cells, cell constituents, and proteins.
Currently, there is no uniform treatment available for SLE. The choice of treatment regimen usually is determined by the individual patient's symptomatology and health status. There is thus the need for a uniform treatment regimen, especially for the nephritic manifestations of SLE.
The present invention provides a method for identifying peptide sequences which bind to anti-dsDNA antibodies. The present invention also provides peptide sequences which define epitopes recognized by pathogenic murine anti-dsDNA antibodies. The present invention also provides an accurate and rapid method of detecting anti-dsDNA antibodies and of diagnosing SLE which can used by unskilled individuals. The methods of detection and diagnosis of the present invention are based on the detection of the complexes formed between the anti-dsDNA antibodies present in a biological sample and one or more of the peptides of the present invention. The present invention further provides a method of treating SLE using one or a mixture of two or more of the peptides of the present invention to block the harmful results which occur whenever the anti-dsDNA antibodies interact with their target in vivo.